The present invention relates to the field of micromanipulation and, more particularly, to a method to and device for physically manipulating small objects, especially living cells. The present invention also relates to the field of life sciences, and more particularly to a device and methods for individually manipulating cells.
In the fields of biology and medicine it is often important to study the results of the interaction between living cells and external factors such as environment, physical stimuli, chemical stimuli and other cells. Such studies are important, for example, for medical diagnostics, drug development and the understanding of basic cell function and are generally divided into two types, static and dynamic studies.
In static studies a group of cells are exposed to whatever stimulus is being studied and, after a certain time, the magnitude and nature of the reaction of the group of cells to the stimulus are determined.
In dynamic studies a single cell or a group of cells is exposed to whatever stimulus is being studied and the magnitude and nature of the reaction of the cell or group to the stimulus are determined, either continuously or discretely.
Both static and dynamic studies are often performed on a population of cells on a macroscopic scale, in cuvettes or well arrays. One disadvantage of studying populations of cells is that the results may teach of secondary effects rather than primary effects of stimuli: the response of a cell to the response of other cells to a stimulus is detected rather than the effect of the stimulus itself. Another disadvantage of such studies is that the results reflect a distribution of effects on a group of cells. This disadvantage is partially overcome by the use of homogenous populations of cells. Although the study of homogenous populations of cells is informative, results are not necessarily representative of “real-life” effects. Although theoretically possible, the required manipulations using available technologies are too difficult and too slow when applied to the study of individual cells.
Static and dynamic studies are also performed using flow cytometry. In flow cytometry, the response of a cell to a stimulus is measured or detected for a single cells moving through a medium, the cell being discarded subsequently to the measurement. Flow-cytometry allows neither the study of an individual cell over a period of time nor the study of the interaction of two or more specifically selected cells.
Practitioners of flow cytometry realize that many critical questions in cell biology, developmental biology, immunology, oncology, pharmacology and virology cannot be answered using even the most sophisticated flow cytometry techniques. It is clear to one skilled in the art that complete understanding of complex biological problem requires the dynamic manipulation and study of single cells or of a multiplicity of cells studied as individuals in parallel or sequentially.
There is thus a widely recognized need for, and it would be highly advantageous to have, a method to manipulate, isolate and study single, whole, living cells as individuals.